Paterson G J, Ohashi Y, Reynolds G P, Pratt J A, Morris B J
Yoshitomi Research Institute of Neuroscience in Glasgow, University of Glasgow, Glasgow, UK.
J Psychopharmacol. 2006 Sep;20(5):636-42. doi: 10.1177/0269881106062025. Epub 2006 Feb 14.
The psychotomimetic drug phencyclidine (PCP) induces symptoms closely related to those of schizophrenia in humans. In order to test the hypothesis that cytokines may be involved in the aetiology and treatment of schizophrenia, this study investigated the levels of cytokine mRNAs in rat brain after acute and chronic administration of PCP, in the presence and absence of antipsychotic drugs. The levels of the mRNAs encoding TNF, IL-2, IL-6, TGF 1, 2, 3, IL-3 and GM-CSF were measured in the prefrontal cortex, cortex, hippocampus, ventral and dorsal striatum regions of male hooded Long Evans rats after acute drug administration. Antipsychotic drugs and PCP significantly reduced the levels of TNF in the prefrontal cortex compared to vehicle-treated animals, whilst other cytokines remained unchanged. In addition, significant reductions in the levels of TNF mRNA in the prefrontal cortex still occurred 24h after acute PCP administration. However, levels of TNF mRNA were restored to control values after chronic PCP treatment, whereas increased expression was detected in animals co-administered with haloperidol. Levels of TNF mRNA were also found to be significantly increased in the prefrontal cortex of schizophrenic subjects. The relationship between TNF levels and schizophrenia are discussed.
拟精神病药物苯环己哌啶（PCP）在人类中诱发的症状与精神分裂症密切相关。为了检验细胞因子可能参与精神分裂症病因和治疗的假说，本研究调查了在给予和不给予抗精神病药物的情况下，急性和慢性给予PCP后大鼠脑中细胞因子mRNA的水平。在雄性长爪沙鼠急性给药后，测量前额叶皮质、皮质、海马体、腹侧和背侧纹状体区域中编码肿瘤坏死因子（TNF）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、转化生长因子1、2、3（TGF 1、2、3）、白细胞介素-3（IL-3）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）的mRNA水平。与溶剂处理的动物相比，抗精神病药物和PCP显著降低了前额叶皮质中TNF的水平，而其他细胞因子保持不变。此外，急性给予PCP后24小时，前额叶皮质中TNF mRNA的水平仍显著降低。然而，慢性给予PCP后，TNF mRNA的水平恢复到对照值，而在联合给予氟哌啶醇的动物中检测到表达增加。在精神分裂症患者的前额叶皮质中也发现TNF mRNA的水平显著升高。本文讨论了TNF水平与精神分裂症之间的关系。
